scholarly journals Lisen&Curate: A platform to facilitate gathering textual evidence for curation of regulation of transcription initiation in bacteria

Author(s):  
Martín Díaz-Rodríguez ◽  
Oscar Lithgow-Serrano ◽  
Francisco Guadarrama-García ◽  
Víctor H. Tierrafría ◽  
Socorro Gama-Castro ◽  
...  
Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stephanie Dobersch ◽  
Karla Rubio ◽  
Indrabahadur Singh ◽  
Stefan Günther ◽  
Johannes Graumann ◽  
...  

AbstractIn addition to nucleosomes, chromatin contains non-histone chromatin-associated proteins, of which the high-mobility group proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of high-mobility group proteins during transcription initiation remain unclear. Here we show that high-mobility group AT-hook 2 protein (HMGA2) induces DNA nicks at the transcription start site, which are required by the histone chaperone FACT complex to incorporate nucleosomes containing the histone variant H2A.X. Further, phosphorylation of H2A.X at S139 (γ-H2AX) is required for repair-mediated DNA demethylation and transcription activation. The relevance of these findings is demonstrated within the context of TGFB1 signaling and idiopathic pulmonary fibrosis, suggesting therapies against this lethal disease. Our data support the concept that chromatin opening during transcriptional initiation involves intermediates with DNA breaks that subsequently require DNA repair mechanisms to ensure genome integrity.


2016 ◽  
Author(s):  
Shan Gao ◽  
Xiaoxuan Tian ◽  
Yu Sun ◽  
Zhenfeng Wu ◽  
Zhi Cheng ◽  
...  

AbstractIn this study, we introduced a general framework to use PacBio full-length transcriptome sequencing for the investigation of the fundamental problems in mitochondrial biology,e.g.genome arrangement, heteroplasmy, RNA processing and the regulation of transcription or replication. As a result, we produced the first full-length human mitochondrial transcriptome from the MCF7 cell line based on the PacBio platform and characterized the human mitochondrial transcriptome with more comprehensive and accurate information. The most important finding was two novel lnRNAs hsa-MDL1 and hsa-MDL1AS, which are encoded by the mitochondrial D-loop regions. We propose hsa-MDL1 and hsa-MDL1AS, as the precursors of transcription initiation RNAs (tiRNAs), belong to a novel class of long non-coding RNAs (lnRNAs), which is named as long tiRNAs (ltiRNAs). Based on the mitochondrial RNA processing model, the primary tiRNAs, precursors and mature tiRNAs could be discovered to completely reveal tiRNAs from their origins to functions. The MDL1 and MDL1AS lnRNAs and their regulation mechanisms exist ubiquitously from insects to human.


2020 ◽  
Author(s):  
Carlos-Francisco Méndez-Cruz ◽  
Martín Díaz-Rodríguez ◽  
Francisco Guadarrama-García ◽  
Oscar Lithgow-Serrano ◽  
Socorro Gama-Castro ◽  
...  

ABSTRACTThe amount of published papers in biomedical research makes it rather impossible for a researcher to keep up to date. This is where machine processing of scientific publications could contribute to facilitate the access to knowledge. How to make use of text mining capabilities and still preserve the high quality of manual curation, is the challenge we focused on. Here we present the Lisen&Curate system designed to enable current and future NLP capabilities within a curation environment interface used in curation of literature on the regulation of transcription initiation in bacteria. The current version extracts regulatory interactions with the corresponding sentences for curators to confirm or reject accelerating their curation. It also uses an embedded metrics of sentence similarity offering the curator an alternative mechanism of navigating through semantically similar sentences within a given paper as well as across papers of a pre-defined corpus of publications pertinent to the task. We show results of the use of the system to curate literature in E. coli as well as literature in Salmonella. A major advantage of the system is to save as part of the curation work, the precise link for every curated piece of knowledge with the corresponding specific sentence(s) in the curated publication supporting it. We discuss future directions of this type of curation infrastructure.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Simona Pilotto ◽  
Thomas Fouqueau ◽  
Natalya Lukoyanova ◽  
Carol Sheppard ◽  
Soizick Lucas-Staat ◽  
...  

AbstractRNA polymerase inhibition plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. Here we present the high-resolution structures of two such RNAP-inhibitor complexes that provide the structural bases underlying RNAP inhibition in archaea. The Acidianus two-tailed virus encodes the RIP factor that binds inside the DNA-binding channel of RNAP, inhibiting transcription by occlusion of binding sites for nucleic acid and the transcription initiation factor TFB. Infection with the Sulfolobus Turreted Icosahedral Virus induces the expression of the host factor TFS4, which binds in the RNAP funnel similarly to eukaryotic transcript cleavage factors. However, TFS4 allosterically induces a widening of the DNA-binding channel which disrupts trigger loop and bridge helix motifs. Importantly, the conformational changes induced by TFS4 are closely related to inactivated states of RNAP in other domains of life indicating a deep evolutionary conservation of allosteric RNAP inhibition.


2021 ◽  
Author(s):  
Finn Werner ◽  
Simona Pilotto ◽  
Thomas Fouqueau ◽  
Natalya Lukoyanova ◽  
Carol Sheppard ◽  
...  

Abstract The inhibition of RNA polymerases activity plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. Here we present the high-resolution structures of two such RNAP-inhibitor complexes that provide the structural basis underlying RNAP inhibition in archaea. The Acidianus two-tailed virus (ATV) encodes the RIP factor that binds to the inside the DNA-binding channel of RNAP, inhibiting transcription by occlusion of binding sites for nucleic acid and the transcription initiation factor TFB. Infection with the Sulfolobus Turreted Icosahedral Virus (STIV) induces the expression of the host factor TFS4, which binds in the RNAP secondary channel similarly to eukaryotic transcript cleavage factors. In contrast to RIP, TFS4 binding allosterically induces a widening of the DNA binding channel which disrupts trigger loop and bridge helix motifs. Importantly, the conformational changes induced by TFS4 are closely related to inactivated states of RNAP in other domains of life indicating a deep evolutionary conservation of allosteric RNAP inhibition.


Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1079
Author(s):  
Aneta Pluta ◽  
Juan P. Jaworski ◽  
Renée N. Douville

Human T-lymphotrophic virus type 1 (HTLV-1) and Bovine leukemia virus (BLV) belong to the Deltaretrovirus genus. HTLV-1 is the etiologic agent of the highly aggressive and currently incurable cancer adult T-cell leukemia (ATL) and a neurological disease HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). BLV causes neoplastic proliferation of B cells in cattle: enzootic bovine leucosis (EBL). Despite the severity of these conditions, infection by HTLV-1 and BLV appear in most cases clinically asymptomatic. These viruses can undergo latency in their hosts. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infection, as well as for pathogenesis in vivo. In this review, we will present the mechanisms that control proviral activation and retroviral latency in deltaretroviruses, in comparison with other exogenous retroviruses. The 5′ long terminal repeats (5′-LTRs) play a main role in controlling viral gene expression. While the regulation of transcription initiation is a major mechanism of silencing, we discuss topics that include (i) the epigenetic control of the provirus, (ii) the cis-elements present in the LTR, (iii) enhancers with cell-type specific regulatory functions, (iv) the role of virally-encoded transactivator proteins, (v) the role of repressors in transcription and silencing, (vi) the effect of hormonal signaling, (vii) implications of LTR variability on transcription and latency, and (viii) the regulatory role of non-coding RNAs. Finally, we discuss how a better understanding of these mechanisms may allow for the development of more effective treatments against Deltaretroviruses.


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